Objectives: This case-control study aimed to investigate the predictors of return to work (RTW) following work-related major forearm, wrist or hand injury at the preparation stage of return to work. Material and Methods: A total of 80 clients were recruited and divided into 2 groups depending on their readiness of RTW. The groups were compared with each other with regard to their demographics, compensation status, hand injury severity, health perception, and time off work (TOW) using correlation coefficient. Predictors of RTW were measured by logistic regression analysis. Results: There were no significant differences in demographics and the severity of hand injury between 2 groups. Self-perceived physical functioning (p = 0.04), vitality (p = 0.01), mental health (p = 0.03) and TOW (p = 0.001) were significantly different between Action group and Preparation group. With binary logistic regression analysis, self-perceived vitality (odds ratio (OR) = 1.041) and TOW (OR = 0.996) were shown to be strongly predictive of RTW at the preparation stage of return to work. Conclusions: This study has shown that shorter TOW and better self-perceived vitality could predict early readiness for RTW after major work-related forearm, wrist or hand injury.